Preview Biochemistry, 9th edition by Shawn O. Farrell Owen M. McDougal Mary K. Campbell (2018) Preview Biochemistry, 9th edition by Shawn O. Farrell Owen M. McDougal Mary K. Campbell (2018) Preview Biochemistry, 9th edition by Shawn O. Farrell Owen M. McDougal Mary K. Campbell (2018) Preview Biochemistry, 9th edition by Shawn O. Farrell Owen M. McDougal Mary K. Campbell (2018) Preview Biochemistry, 9th edition by Shawn O. Farrell Owen M. McDougal Mary K. Campbell (2018)
Trang 2BIO CHEMISTRY
Trang 5Printed in the United States of America
Print Number: 01 Print Year: 2016
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Biochemistry, Ninth Edition
Mary Campbell, Shawn O Farrell, Owen
McDougal
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Trang 6This book is dedicated to the memory of Mary Campbell, who was
passionately involved in its creation Her avid interest in writing and devotion to student engagement led to the publication of the first eight highly successful editions of this textbook.
—Mary K Campbell
To the returning adult students in my classes, especially those with
children and a full-time job my applause.
—Shawn O Farrell
My recognition and appreciation go to those who saw the potential in me that has taken so many years to develop, and to those students who are on the path to fulfilling their dreams.
—Owen M McDougal
Trang 7of interest included researching the physical chemistry of biomolecules, specifically, spectroscopic studies of protein–nucleic acid interactions
Shawn O Farrell
Shawn O Farrell grew up in northern California and received a B.S degree in biochemistry from the University of California, Davis, where he studied carbohydrate metabolism He completed his Ph.D in biochemistry at Michigan State University, where
he studied fatty acid metabolism For 18 years, Shawn worked at Colorado State University teaching undergraduate biochemistry lecture and laboratory courses Because of his interest in biochemical education, Shawn has written a number of scientific journal articles
about teaching biochemistry He is the coauthor (with Lynn E Taylor) of Experiments in Biochemistry: A Hands-On Approach Shawn became interested in biochemistry while in
college because it coincided with his passion for bicycle racing An active outdoorsman, Shawn raced competitively for 17 years and now officiates at bicycle races around the world He was the technical director of USA Cycling, the national governing body of bicycle racing in the United States for 11 years before returning to teaching at CSU in Pueblo, Colorado He is also an avid fly fisherman, a third-degree black belt in Tae Kwon Do, and a first-degree black belt in combat hapkido Shawn has also written articles on fly fishing for
Salmon Trout Steelheader magazine His other passions are music and foreign languages He
is fluent in Spanish and French and is currently learning to play the guitar
On his fiftieth birthday, he had his first downhill skiing lesson and now cannot get enough of it Never tired of education, he visited CSU again, this time from the other side of the podium, and earned his Master of Business Administration in 2008
Owen M McDougal
Owen M McDougal is a professor of chemistry and biochemistry at Boise State University
He is a native of upstate New York where he earned chemistry degrees at State University of New York at Morrisville (AS) and Oswego (BS) His love of the outdoors motivated him to travel west for graduate school and pursue a PhD at the University of Utah in the laboratory
of C Dale Poulter His work to elucidate the three-dimensional structures of neuropeptides
by nuclear magnetic resonance spectroscopy involved the application of physical chemistry
to address problems in biological systems Graduate studies in the heart of the Wasatch Mountains in Utah led to his lifelong enthusiasm for mountain biking and telemark skiing
In this capacity, Owen tested his skills at competitive mountain bike racing and pursued what resulted in a ten-year stint on the National Ski Patrol Upon completion of his PhD, Owen sought an academic environment that allowed him to share his passion for science with students in small classes He taught general, organic, and biological chemistry at Southern Oregon University, which allowed him to hone his instructional skills Looking
to advance his love for writing, Owen shifted to a faculty position in the research intensive environment at Boise State University, where he investigates the bioactivity of marine and terrestrial natural products, including studies of food chemistry, nutraceutical products, and specialty chemicals Owen lives in Boise, Idaho, with wife Lynette, daughters McKenzie and Riley, dog Tater, cat Melody, tortoise Touché, and rabbit Bixby
Trang 8Brief Contents
2 Water: The Solvent for Biochemical Reactions 33
5 Protein Purification and Characterization Techniques 114
7 The Behavior of Proteins: Enzymes, Mechanisms, and Control 168
8 Lipids and Proteins Are Associated in Biological Membranes 201
9 Nucleic Acids: How Structure Conveys Information 239
11 Transcription of the Genetic Code: The Biosynthesis of RNA 300
12 Protein Synthesis: Translation of the Genetic Message 347
15 The Importance of Energy Changes and Electron Transfer in Metabolism 467
18 Storage Mechanisms and Control in Carbohydrate Metabolism 550
20 Electron Transport and Oxidative Phosphorylation 609
24 Integration of Metabolism: Cellular Signaling 732
Trang 10Organization of Cells 1
1-1 Basic Themes 1
1-2 Chemical Foundations of Biochemistry 2
1-3 The Beginnings of Biology 6
1-4 The Biggest Biological Distinction—
Prokaryotes and Eukaryotes 16
1-5 How We Classify Eukaryotes
and Prokaryotes 21
1A BIOCHEMICAL CONNECTIONS BIOTECHNOLOGY
Extremophiles: The Toast of the Industry 23
2A BIOCHEMICAL CONNECTIONS CHEMISTRY
How Basic Chemistry Affects Life: The Importance of the
2C BIOCHEMICAL CONNECTIONS CHEMISTRY OF BLOOD
Some Physiological Consequences of Blood Buffering 54
2D BIOCHEMICAL CONNECTIONS ACIDS AND SPORTS
Lactic Acid—Not Always the Bad Guy 55
Summary 56
Review Exercises 57
Further Reading 59
Amino Acids and Peptides 60
3-1 Amino Acids Are Three-Dimensional 60
3-2 Structures and Properties of Amino Acids 61
3-3 Amino Acids Can Act as Both Acids and Bases 66
3-4 The Peptide Bond 70 3-5 Small Peptides with Physiological Activity 72
3A BIOCHEMICAL CONNECTIONS PHYSIOLOGY Peptide Hormones—Small Molecules with Big Effects 73
Summary 74Review exercises 75Further Reading 77
The Three-Dimensional Structure of Proteins 78
4-1 Protein Structure and Function 78 4-2 Primary Structure of Proteins 79 4-3 Secondary Structure of Proteins 79 4-4 Tertiary Structure of Proteins 87 4-5 Quaternary Structure of Proteins 93
4A BIOCHEMICAL CONNECTIONS MEDICINE Sickle Cell Anemia 98
Protein Purification and Characterization Techniques 114
5-1 Extracting Pure Proteins from Cells 114 5-2 Column Chromatography 117
5-3 Electrophoresis 123 5-4 Determining the Primary Structure of a Protein 125 5-5 Protein Detection Techniques 131
5A BIOCHEMICAL CONNECTIONS INSTRUMENTATION
The Power of Mass Spectrometry 131
Trang 116-1 Enzyme Kinetics vs Thermodynamics 141
6A BIOCHEMICAL CONNECTIONS HEALTH SCIENCES
Enzymes as Markers for Disease 144
6-2 Rate of Enzyme-Catalyzed Reactions 144
6-3 Enzyme–Substrate Binding 146
6-4 The Michaelis–Menten Approach to Enzyme
Kinetics 148
6B BIOCHEMICAL CONNECTIONS NEUROSCIENCE
Enzyme Lets You Enjoy Champagne 155
6C BIOCHEMICAL CONNECTIONS PHYSICAL ORGANIC
CHEMISTRY
Practical Information from Kinetic Data 155
6-5 Examples of Enzyme-Catalyzed Reactions 156
6-6 Enzyme Inhibition 157
6D BIOCHEMICAL CONNECTIONS MEDICINE
Enzyme Inhibition in the Treatment of AIDS 163
Summary 164
Review Exercises 164
Further Reading 167
The Behavior of Proteins: Enzymes,
Mechanisms, and Control 168
7-1 Behavior of Allosteric Enzymes 168
7-2 The Concerted and Sequential Models for Allosteric
Enzymes 172
7A BIOCHEMICAL CONNECTIONS MEDICINE
Allosterism: Drug Companies Exploit the Concept 175
7-3 Control of Enzyme Activity by Phosphorylation 176
7B BIOCHEMICAL CONNECTIONS MEDICINE
An Ancient Drug Works by Stimulating a Protein Kinase 178
7-4 Zymogens 179
7-5 The Nature of the Active Site 180
7C BIOCHEMICAL CONNECTIONS ALLIED HEALTH
Families of Enzymes: Proteases 182
7-6 Chemical Reactions Involved in Enzyme Mechanisms 185
7-7 The Active Site and Transition States 188
7D BIOCHEMICAL CONNECTIONS ALLIED HEALTH
Catalytic Antibodies against Cocaine 189
7-8 Coenzymes 191
7E BIOCHEMICAL CONNECTIONS ENVIRONMENTAL
TOXICOLOGY
Catalysts for Green Chemistry 193
HOT TOPIC Alzheimer’s Disease 194
Summary 198Review Exercises 198Further Reading 200
Lipids and Proteins Are Associated
in Biological Membranes 201
8-1 The Definition of a Lipid 201 8-2 The Chemical Natures of the Lipid Types 201 8-3 Biological Membranes 208
8A BIOCHEMICAL CONNECTIONS NUTRITION Butter versus Margarine–Which Is Healthier? 211 8B BIOCHEMICAL CONNECTIONS BIOTECHNOLOGY Membranes in Drug Delivery 212
8-4 Membrane Proteins 213 8-5 The Functions of Membranes 216
8C BIOCHEMICAL CONNECTIONS PHYSIOLOGY Lipid Droplets Are Not Just Great Balls of Fat 220
8-6 Lipid-Soluble Vitamins and Their Functions 222
8D BIOCHEMICAL CONNECTIONS NEUROSCIENCE Vision Has Great Chemistry 224
8-7 Prostaglandins and Leukotrienes 228
8E BIOCHEMICAL CONNECTIONS NUTRITION Why Should We Eat More Salmon? 229
HOT TOPIC The Science of Happiness and Depression 231
Summary 236Review Exercises 237Further Reading 238
Nucleic Acids: How Structure Conveys Information 239
9-1 Levels of Structure in Nucleic Acids 239 9-2 The Covalent Structure of Polynucleotides 239
9A BIOCHEMICAL CONNECTIONS LAW Who Owns Your Genes? 244
9-3 The Structure of DNA 245
9B BIOCHEMICAL CONNECTIONS GENETICS The Human Genome Project: Treasure or Pandora’s Box? 252
9-4 Denaturation of DNA 253 9-5 The Principal Kinds of RNA and Their Structures 254 9-6 Roles for RNA 256
9-7 RNA and Medical Applications 260
9C BIOCHEMICAL CONNECTIONS GENETICS Why Identical Twins Are Not Identical 262
HOT TOPIC The Genetics of Breast Cancer 263
Summary 265Review Exercises 266Further Reading 268
6
7
8
9
Trang 1210-4 Proteins Required for DNA Replication 278
10-5 Proofreading and Repair 282
10A BIOCHEMICAL CONNECTIONS GENETICS
Why Does DNA Contain Thymine and Not Uracil? 287
10-6 DNA Recombination 288
10B BIOCHEMICAL CONNECTIONS MICROBIOLOGY
The SOS Response in E coli 290
10-7 Eukaryotic DNA Replication 291
10C BIOCHEMICAL CONNECTIONS ALLIED HEALTH
Telomerase and Cancer 295
10D BIOCHEMICAL CONNECTIONS EVOLUTIONARY
11-3 Transcription Regulation in Prokaryotes 306
11A BIOCHEMICAL CONNECTIONS BACTERIOLOGY
Riboswitches Provide Another Weapon against Pathogens 315
11-4 Transcription in Eukaryotes 316
11-5 Transcription Regulation in Eukaryotes 321
11-6 Noncoding RNAs 326
11B BIOCHEMICAL CONNECTIONS MEDICINE
A Micro RNA Helps Regenerate Nerve Synapses after Injury 329
11-7 Structural Motifs in DNA-Binding Proteins 330
11-8 Posttranscriptional RNA Modifications 333
12-1 Translating the Genetic Message 347
12-2 The Genetic Code 347
12A BIOCHEMICAL CONNECTIONS VIROLOGY
Influenza A Virus Alters the Reading Frame to Lower Its
12B BIOCHEMICAL CONNECTIONS NEUROLOGY Protein Synthesis Makes Memories 368
12-6 Posttranslational Modification of Proteins 370
12C BIOCHEMICAL CONNECTIONS GENETICS Silent Mutations Are Not Always Silent 371 12D BIOCHEMICAL CONNECTIONS BIOPHYSICAL CHEMISTRY
Chaperones: Preventing Unsuitable Associations 373
12-7 Protein Degradation 374
12E BIOCHEMICAL CONNECTIONS PHYSIOLOGY How Do We Adapt to High Altitude? 375
Summary 376Review Exercises 377Further Reading 379
Nucleic Acid Biotechnology Techniques 380
13-1 Purification and Detection of Nucleic Acids 38013-2 Restriction Endonucleases 382
13-3 Cloning 38513-4 Genetic Engineering 391
13A BIOCHEMICAL CONNECTIONS PLANT SCIENCE Genetic Engineering in Agriculture 392
13B BIOCHEMICAL CONNECTIONS ALLIED HEALTH Human Proteins through Genetic Recombination Techniques 396
13-5 DNA Libraries 398
13C BIOCHEMICAL CONNECTIONS ANALYTICAL CHEMISTRY (CHROMATOGRAPHY)
Fusion Proteins and Fast Purifications 399
13-6 The Polymerase Chain Reaction 40113-7 DNA Fingerprinting 404
13D BIOCHEMICAL CONNECTIONS FORENSICS CSI: Biochemistry—Forensic Uses of DNA Testing 408
13-8 Sequencing DNA 40813-9 Genomics and Proteomics 410
HOT TOPIC CRISPR 415
Summary 417Review Exercises 419Further Reading 420
Viruses, Cancer, and Immunology 422
14-1 Viruses 42214-2 Retroviruses 427
14A BIOCHEMICAL CONNECTIONS MEDICINE Viruses Are Used for Gene Therapy 428
13
14
Trang 13xii Contents
14-3 The Immune System 429
14B BIOCHEMICAL CONNECTIONS MEDICINE
The First Vaccine: Bad Science Gone Good 430
14C BIOCHEMICAL CONNECTION VIROLOGY
Viral RNAs Outwit the Immune System 442
14-4 Cancer 442
14D BIOCHEMICAL CONNECTIONS GENETICS
Cancer: The Dark Side of the Human Genome 443
14E BIOCHEMICAL CONNECTIONS BIOTECHNOLOGY
Nanotech Tackles Cancer 450
14F BIOCHEMICAL CONNECTIONS IMMUNOLOGY
The Importance of Energy
Changes and Electron Transfer in
Metabolism 467
15-1 Standard States for Free-Energy Changes 467
15-2 A Modified Standard State for Biochemical
Applications 470
15-3 The Nature of Metabolism 471
15A BIOCHEMICAL CONNECTIONS THERMODYNAMICS
Living Things Are Unique Thermodynamic Systems 471
15-4 The Role of Oxidation and Reduction in
Metabolism 472
15-5 Coenzymes in Biologically Important
Oxidation-Reduction Reactions 473
15-6 Coupling of Production and Use of Energy 477
15B BIOCHEMICAL CONNECTIONS PHYSIOLOGY
ATP in Cell Signaling 480
15-7 Coenzyme A in Activation of Metabolic
16-1 Sugars: Their Structures and Stereochemistry 490
16A BIOCHEMICAL CONNECTIONS NUTRITION AND
HEALTH
Low-Carbohydrate Diets 495
16-2 Reactions of Monosaccharides 498
16B BIOCHEMICAL CONNECTIONS NUTRITION
Vitamin C is Related to Sugars 499
15
16
16-3 Some Important Oligosaccharides 504
16C BIOCHEMICAL CONNECTIONS NUTRITION Lactose Intolerance: Why Do So Many People Not Want
to Drink Milk? 506
16-4 Structures and Functions of Polysaccharides 507
16D BIOCHEMICAL CONNECTIONS ALLIED HEALTH Why Is Dietary Fiber So Good for You? 508
16-5 Glycoproteins 514
16E BIOCHEMICAL CONNECTIONS ALLIED HEALTH Glycoproteins and Blood Transfusions 515
Summary 516Review Exercises 517Further Reading 519
Glycolysis 520
17-1 The Overall Pathway of Glycolysis 520
17A BIOCHEMICAL CONNECTIONS ENVIRONMENTAL SCIENCE
Biofuels from Fermentation 521
17-2 Conversion of Six-Carbon Glucose to Three-Carbon Glyceraldehyde-3-Phosphate 524
17B BIOCHEMICAL CONNECTIONS ALLIED HEALTH Dolphins as a Model for Humans with Diabetes 528
17-3 Glyceraldehyde-3-Phosphate Is Converted to Pyruvate 531
17-4 Anaerobic Metabolism of Pyruvate 538
17C BIOCHEMICAL CONNECTIONS ALLIED HEALTH (Dentistry)
What Is the Connection between Anaerobic Metabolism and Dental Plaque? 539
17D BIOCHEMICAL CONNECTIONS ALLIED HEALTH Fetal Alcohol Syndrome 542
17E BIOCHEMICAL CONNECTIONS CANCER RESEARCH Using Pyruvate Kinase Isozymes to Treat Cancer 543
17-5 Energy Production in Glycolysis 54317-6 Control of Glycolysis 544
Summary 547Review Exercises 548Further Reading 549
Storage Mechanisms and Control
in Carbohydrate Metabolism 550
18-1 How Glycogen Is Degraded and Produced 550
18A BIOCHEMICAL CONNECTIONS EXERCISE PHYSIOLOGY
Why Do Athletes Go in for Glycogen Loading? 552
18-2 Gluconeogenesis Produces Glucose from Pyruvate 557
18-3 Control of Carbohydrate Metabolism 562
17
18
Trang 14Contents xiii
18-4 Glucose Is Sometimes Diverted through the Pentose
Phosphate Pathway 570
18B BIOCHEMICAL CONNECTIONS ALLIED HEALTH
The Pentose Phosphate Pathway and Hemolytic Anemia 573
Summary 575
Review Exercises 575
Further Reading 577
The Citric Acid Cycle 578
19-1 The Central Role of the Citric Acid Cycle in
Metabolism 578
19-2 The Overall Pathway of the Citric Acid Cycle 578
19-3 How Pyruvate is Converted to Acetyl-CoA 580
19-4 The Individual Reactions of the Citric Acid Cycle 584
19A BIOCHEMICAL CONNECTIONS TOXICOLOGY
Fluorine Compounds and Carbohydrate Metabolism 586
19B BIOCHEMICAL CONNECTIONS LABELING METHODS
What Is the Origin of the CO 2 Released by the Citric Acid
Cycle? 588
19-5 Energetics and Control of the Citric Acid Cycle 593
19-6 The Glyoxylate Cycle: A Related Pathway 596
19-7 The Citric Acid Cycle in Catabolism 597
19-8 The Citric Acid Cycle in Anabolism 598
19C BIOCHEMICAL CONNECTIONS EVOLUTION
Why Can’t Animals Use All the Same Energy Sources as Plants
and Bacteria? 599
19D BIOCHEMICAL CONNECTION NUTRITION
Why Is It So Hard to Lose Weight? 602
19-9 The Link to Oxygen 604
20-1 The Role of Electron Transport in Metabolism 609
20-2 Reduction Potentials in the Electron Transport
Chain 610
20-3 Organization of Electron Transport Complexes 613
20-4 The Connection between Electron Transport
and Phosphorylation 620
20-5 The Mechanism of Coupling in Oxidative
Phosphorylation 622
20-6 Shuttle Mechanisms 625
20A BIOCHEMICAL CONNECTIONS ALLIED HEALTH
Sports and Metabolism 627
20-7 The ATP Yield from Complete Oxidation
Lipid Metabolism 636
21-1 Lipids Are Involved in the Generation and Storage
of Energy 63621-2 Catabolism of Lipids 63621-3 The Energy Yield from the Oxidation of Fatty Acids 641
21-4 Catabolism of Unsaturated Fatty Acids and Carbon Fatty Acids 643
Odd-21-5 Ketone Bodies 64621-6 Fatty Acid Biosynthesis 647
21A BIOCHEMICAL CONNECTIONS GENE EXPRESSION Transcription Activators in Lipid Biosynthesis 647
21B BIOCHEMICAL CONNECTIONS NUTRITION Acetyl-CoA Carboxylase—A New Target in the Fight against Obesity 650
21C BIOCHEMICAL CONNECTIONS GENETICS
A Gene for Obesity 655
21-7 Synthesis of Acylglycerols and Compound Lipids 65521-8 Cholesterol Biosynthesis 659
21D BIOCHEMICAL CONNECTIONS ALLIED HEALTH Atherosclerosis 667
21-9 Hormonal Control of Appetite 669
Summary 671Review Exercises 672Further Reading 673
Photosynthesis 675
22-1 Chloroplasts Are the Site of Photosynthesis 675
22A BIOCHEMICAL CONNECTIONS PHYSICS The Relationship between Wavelength and Energy of Light 678
22-2 Photosystems I and II and the Light Reactions of Photosynthesis 679
22-3 Photosynthesis and ATP Production 68522-4 Evolutionary Implications of Photosynthesis with and without Oxygen 686
22B BIOCHEMICAL CONNECTIONS APPLIED GENETICS Improving the Yield of Antimalarial Plants 688
22-5 Dark Reactions of Photosynthesis Fix CO2 688
22C BIOCHEMICAL CONNECTIONS AGRICULTURE Plants Feed Animals—Plants Need Energy—Plants Can Produce Energy 688
22D BIOCHEMICAL CONNECTIONS GENETICS Chloroplast Genes 694
21
22
Trang 15The Metabolism of Nitrogen 701
23-1 Nitrogen Metabolism: An Overview 701
23-2 Nitrogen Fixation 702
23A BIOCHEMICAL CONNECTIONS PLANT SCIENCE
Why Is the Nitrogen Content of Fertilizers So Important? 704
23-3 Feedback Inhibition in Nitrogen Metabolism 704
23-4 Amino Acid Biosynthesis 705
23-5 Essential Amino Acids 713
23-6 Amino Acid Catabolism 713
23B BIOCHEMICAL CONNECTIONS PHYSIOLOGY
Water and the Disposal of Nitrogen Wastes 715
23C BIOCHEMICAL CONNECTIONS MEDICINE
Chemotherapy and Antibiotics—Taking Advantage of the
Need for Folic Acid 728
24-1 Connections between Metabolic Pathways 732
24A BIOCHEMICAL CONNECTIONS ALLIED HEALTH Alcohol Consumption and Addiction 733
24-2 Biochemistry and Nutrition 734
24B BIOCHEMICAL CONNECTIONS NUTRITION Iron: An Example of a Mineral Requirement 737
24-3 Hormones and Second Messengers 74124-4 Hormones and the Control of Metabolism 749
24C BIOCHEMICAL CONNECTIONS NUTRITION Insulin and Low-Carbohydrate Diets 751
24-5 Insulin and Its Effects 752
24D BIOCHEMICAL CONNECTIONS ALLIED HEALTH
A Workout a Day Keeps Diabetes Away? 754 24E BIOCHEMICAL CONNECTIONS ALLIED HEALTH Insulin, Diabetes, and Cancer 755
HOT TOPIC G-Protein–Coupled Receptors 757
Summary 761Review Exercises 762Further Reading 764Answers to Review Exercises A-1 Index I-1
24
Trang 16This text is intended for students in any field of science or engineering who
want a one-semester introduction to biochemistry but who do not intend to
be biochemistry majors Our main goal in writing this book is to make
bio-chemistry as clear and applied as possible and to familiarize science students with
the major aspects of biochemistry For students of biology, chemistry, physics,
geol-ogy, nutrition, sports physiolgeol-ogy, and agriculture, biochemistry impacts greatly on
the content of their fields, especially in the areas of medicine and biotechnology
For engineers, studying biochemistry is especially important for those who hope
to enter a career in biomedical engineering or some form of biotechnology
Students who will use this text are at an intermediate level in their studies
A beginning biology course, general chemistry, and at least one semester of
organic chemistry are assumed as preparation
What’s New
All textbooks evolve to meet the interests and needs of students and instructors
and to include the most current information Several changes mark this edition
Biochemistry Hot Topics These articles are
now conveniently located within the relevant chapters
They highlight new breakthroughs and topics in the area
of biochemistry such as CRISPR, Alzheimer’s disease,
epigenetics, brown fat, and more!
Updated Coverage Each chapter in the text has been updated with the current developments and scientific findings in the biochemistry field
New Design and Updated Art Illustrations throughout the text have been redrawn for improved consistency In conjunction with the book’s updated art program, a more contemporary design and color palette have been utilized
Further Reading An annotated bibliography is now provided in the Further Reading section at the end of each chapter, making these resources more easily accessible to the student
Preface
UPDATED
xv
want a one-semester introduction to biochemistry but who do not intend to
be biochemistry majors Our main goal in writing this book is to make
bio-chemistry as clear and applied as possible and to familiarize science students with
the major aspects of biochemistry For students of biology, chemistry, physics,
geol-ogy, nutrition, sports physiolgeol-ogy, and agriculture, biochemistry impacts greatly on
the content of their fields, especially in the areas of medicine and biotechnology
For engineers, studying biochemistry is especially important for those who hope
to enter a career in biomedical engineering or some form of biotechnology
Students who will use this text are at an intermediate level in their studies
A beginning biology course, general chemistry, and at least one semester of
organic chemistry are assumed as preparation
What’s New
All textbooks evolve to meet the interests and needs of students and instructors
and to include the most current information Several changes mark this edition
Biochemistry Hot Topics These articles are
now conveniently located within the relevant chapters
They highlight new breakthroughs and topics in the area
of biochemistry such as CRISPR, Alzheimer’s disease,
epigenetics, brown fat, and more!
text has been updated with the current developments and scientific findings in the biochemistry field
New Design and Updated Art
Illustrations throughout the text have been redrawn for improved consistency In conjunction with the consistency
book’s updated art program, a more contemporary design and color palette have been utilized
bibliography is now provided in the Further Reading section at the end of each chapter, making these resources each chapter
more easily accessible to the student
Preface
UPDATED
HOT TOPIC
HT-415
M
HOT
enetic engineering is the process
by which scientists use nology to manipulate the DNA of an genes or inserting/deleting mutations to genetic engineering introduced earlier in Researchers at J R Simplot Co inserted genes from the wild potato into the ge- nome of the Innate potato to eliminate browning and bruising The three most edit a genome are (1) clustered, regularly technology in combination with the Cas9
biotech-(2) site-directed zinc finger nucleases;
segment will focus on the most recent, powerful, broadly applicable, and poten- tially impactful of these biotechnological advancements: the CRISPR/Cas9 ge- tive, site-directed zinc finger nucleases difficulties in the design of proteins that effector nucleases are challenged due to design, synthesis, and validation of pro- teins required as engineered nucleases
CRISPR/Cas9 is an RNA-based nome editing strategy employing the same cellular machinery used by bacte- ria to afford them immunity to viruses or
ge-plasmids CRISPR was first described in
1987 and fundamental research was formed on the genome editing approach when it was demonstrated that CRISPR/ Cas9 RNA-guided DNA endonuclease genome engineering in eukaryotic cells over 1,000 studies have been published
per-in the scientific literature and the damental research on in vitro model testing To understand how genome works, let’s first begin with the four key sgRNA, and PAM (Table 13.2).
fun-G
Table 13.2 Components of the CRISPR/Cas9 genome editing system.
Acronym Spelled out Significance Image CRISPR Clustered
Interspaced Palindromic Repeats
Loci on DNA that can serve as gene insertion or deletion positions cas genes Leader
Repeat-spacer array
Cas9 CRISPR associated protein 9 Nuclease for cutting DNA (Cas 1 10 exist)
sgRNA Single guide ribonucleic acid A construct/chimera of CRISPR RNA
RNA (tracrRNA); contains sequence information for insertion/deletion
sgRNA (single guide RNA)
Target-specific crRNA sequence tracrRNA
PAM Protospacer adjacent motif sgRNA binds to a target gene locus next to PAM; sequence NGG (any, guanine,
adenine, guanine) in humans
Trang 17read in each chapter And although they have a different presentation than the rest of the narrative, they are meant to
be read with the narrative and should not be skipped They are like crescendos in classical music—the change in tempo from the usual narrative to the unique visual presentation and voice
of the Biochemical Connections prevents the student’s level
of interest from dipping—students are always engaged See a full listing of Biochemical Connections boxes in the Table of Contents
Apply Your Knowledge The Apply Your Knowledge boxes are interspersed within chapters and are designed to provide students with problem-solving experience The topics chosen are areas of study where students usually have the most difficulty Solutions and problem-solving strategies are included, giving examples of the problem-solving approach for specific material
Adenylate cyclase Receptor
cAMP Hormone
Protein kinase
(inactive) Protein kinase(active)
Triacylglycerol lipase (inactive) Triacylglycerol lipase (active)
DAG lipase Fatty acid
Fatty acid
Adipose cell
Plasma membrane
Fatty acid ADP
Biochemical Connections The Biochemical Connections highlight special topics of particular interest to students Topics frequently have clinical implications, such as cancer, AIDS, and nutrition These essays help students make the connection between biochemistry and the real-world They are flowed in with the narrative and are placed exactly where they need to be
read in each chapter And although they have a different presentation than the rest of the narrative, they are meant to
be read with the narrative and should not be skipped They are like crescendos in classical music—the change in tempo from the usual narrative to the unique visual presentation and voice
of the Biochemical Connections prevents the student’s level
of interest from dipping—students are always engaged See a full listing of Biochemical Connections boxes in the Table of Contents
Apply Your Knowledge The Apply Your Knowledge boxes are interspersed within chapters and are designed to provide students with problem-solving experience The topics chosen are areas of study where students usually have the most difficulty Solutions and problem-solving strategies are included, giving examples of the problem-solving approach for specific material
Adenylate cyclase Receptor
cAMP Hormone
Protein kinase
(inactive) Protein kinase(active)
Triacylglycerol lipase (inactive) Triacylglycerol lipase (active) Phosphatase
Triacylglycerol
Diacylglycerol
Monoacylglycerol Glycerol
MAG lipase
DAG lipase Fatty acid
Fatty acid
Adipose cell
Plasma membrane
Fatty acid ADP
AT
ATP
AT ATP
P P
P P
and its social effects, added four new Review
Exercises
diseases, added Hot Topic about aging
markers for diseases
added four new Review Exercises
depression, added two new Review Exercises
material on long noncoding RNA, added new
section on medical applications of RNA, deleted
Biochemical Connection on synthetic genome
Biochemical Connections box about CREB,
deleted Biochemical Connections about
epigenetics and cancer
interspaced, short palindromic repeat technology
in combination with the Cas9 RNA-guided nuclease (CRISPR/Cas9) method of genetic engineering, example of CRISPR/Cas9 to engineer Innate potato
Ebola and advances in stem cell research
of artificial sweeteners to gut microbiome, suggesting the reason diet products may not result in weight loss
1080 (sodium fluoroacetate) for control of mammal populations in New Zealand
recent research developments demonstrating the benefits of brown adipose tissue to maintenance
of healthy metabolism
coupled receptors to include recent research
on the biased agonism or functional selectivity model associated with opioid receptors
12B BIOCHEMICAL CONNECTIONS
Neurology
Protein Synthesis Makes Memories
2.1 APPLY YOUR KNOWLEDGE
pH Calculations
Trang 18Preface xvii
Marginal Glossary No flipping back and forth to read full definitions of key
terms Terms are defined in the margins
Early Inclusion of Thermodynamics Select material on thermodynamics
appears early in the text Chapter 1 includes sections on energy and change,
spontaneity in biochemical reactions, and life and thermodynamics Also,
Chapter 4 contains an extended section on protein-folding dynamics We
feel it is critical that students understand the driving force of biological
processes and see that so much of biology (protein folding, protein–protein
interactions, small molecule binding, etc.) is driven by the favorable
disordering of water molecules
Summaries and Questions Each chapter closes with a concise
summary, a broad selection of questions, and an annotated
bibliography that suggests sources for further reading The Review
Exercises fall into four categories: RECALL, REFLECT AND APPLY, BIOCHEMICAL
CONNECTIONS, and MATHEMATICAL The RECALL questions are designed for
students to quickly assess their mastery of the material, and the REFLECT AND
APPLY questions are for students to work through more thought-provoking
questions BIOCHEMICAL CONNECTIONS questions test students on the BIOCHEMICAL
CONNECTIONS essays in that chapter The MATHEMATICAL questions are
quantitative in nature and focus on calculations
Organization
Because biochemistry is a multidisciplinary science, the first task in presenting
it to students of widely varying backgrounds is to put it in context The text is
organized into four categories The first provides the necessary background
and connects biochemistry to other sciences The next focuses on the structure
and dynamics of important cellular components This is followed by molecular
biology and then intermediary metabolism
Chapters 1 & 2: Background and Connections
● Relationship between biochemistry and other sciences, particularly
concerning the origins of life
● Organic functional groups in the context of biochemistry
● Link between biochemistry and biology, especially the distinction
between prokaryotes and eukaryotes and the role of organelles in
eukaryotes
● Biochemical view of buffers, solvent properties of water, and other
familiar general chemistry topics
BiochemistryGeology
Astronomy
Physics
Biology
Preface xvii
Marginal Glossary No flipping back and forth to read full definitions of key
terms Terms are defined in the margins
Early Inclusion of Thermodynamics Select material on thermodynamics
appears early in the text Chapter 1 includes sections on energy and change,
spontaneity in biochemical reactions, and life and thermodynamics Also,
Chapter 4 contains an extended section on protein-folding dynamics We
feel it is critical that students understand the driving force of biological
processes and see that so much of biology (protein folding, protein–protein
interactions, small molecule binding, etc.) is driven by the favorable
disordering of water molecules
Summaries and Questions Each chapter closes with a concise
summary, a broad selection of questions, and an annotated
bibliography that suggests sources for further reading The Review
CONNECTIONS, and MATHEMATICAL The RECALL questions are designed for
APPLY LY L questions are for students to work through more thought-provoking
CONNECTIONS essays in that chapter The MATHEMATICAL questions are
quantitative in nature and focus on calculations
Organization
Because biochemistry is a multidisciplinary science, the first task in presenting
it to students of widely varying backgrounds is to put it in context The text is
organized into four categories The first provides the necessary background
and connects biochemistry to other sciences The next focuses on the structure
and dynamics of important cellular components This is followed by molecular
biology and then intermediary metabolism
Chapters 1 & 2: Background and Connections
concerning the origins of life
between prokaryotes and eukaryotes and the role of organelles in
eukaryotes
familiar general chemistry topics
BiochemistryGeology
Trang 19● Thermodynamics, hydrophobic interactions
● Techniques for isolating and studying proteins
● Enzyme kinetics and mechanisms
● Structure of membranes and their lipid components
Chapters 9-14: Molecular Biology
● Replication of DNA
● Transcription and gene regulation
● Biosynthesis of nucleic acids
● Translation of the genetic message and protein synthesis
● Overview of the metabolic pathways: glycolysis
● Glycogen metabolism, gluconeogenesis, and the pentose phosphate pathway
● Citric acid cycle, electron transport chain, and oxidative phosphorylation
● Catabolic and anabolic aspects of lipid metabolism
● Photosynthesis and carbohydrate metabolism
● Plant origin of antimalarials
● Metabolism of nitrogen-containing compounds such as amino acids, porphyrins, and nucleobases
● Integrated look at metabolism, including a treatment of hormones and second messengers
● Nutrition
● Immune systemSome topics such as enzymes and the biosynthesis of nucleic acids are split into two chapters to give students ample time to fully understand the concepts involved Some are discussed several times, such as the control of carbohydrate metabolism Subsequent discussions make use of and build on information students have already learned It is particularly useful to return
to a topic after students have had time to assimilate and reflect on it
This text gives an overview of important topics of interest to biochemists and shows how the remarkable recent progress of biochemistry impinges on other sciences The length is intended to provide instructors with a choice of favorite topics without being overwhelming for the limited amount of time available in one semester
xviii Preface
Chapters 3-8: Structure and Dynamics of Cellular Components
and action of proteins, including enzyme catalysis
interactions
studying proteins
lipid components
Chapters 9-14: Molecular Biology
Chapters 15-24: Intermediary Metabolism
coupled reactions
reduction) reactions
pathway
porphyrins, and nucleobases
to a topic after students have had time to assimilate and reflect on it
This text gives an overview of important topics of interest to biochemists and shows how the remarkable recent progress of biochemistry impinges on other sciences The length is intended to provide instructors with a choice of favorite topics without being overwhelming for the limited amount of time available in one semester
Trang 20Preface xix
Alternative Teaching Options
The order in which individual chapters are covered can be changed to suit the
needs of specific groups of students Although we prefer an early discussion
of thermodynamics, the portions of Chapters 1 and 4 that deal with
thermo-dynamics can be covered at the beginning of Chapter 15 All of the molecular
biology chapters (Chapters 9 through 14) can precede metabolism or can
fol-low it, depending on the instructor’s choice The order in which the material
on molecular biology is treated can be varied according to the preference of
the instructor
Alternate Editions
Loose-Leaf Edition for Biochemistry 9e
ISBN: 978-1-305-96195-1
A loose-leaf (unbound, three-hole-punched) version of Biochemistry 9e, which
can be inserted in a binder, is also available
Acknowledgments
We would like to acknowledge colleagues who contributed their ideas and
critiques of the manuscript Some reviewers responded to specific queries
regarding the text itself We thank them for their efforts and their helpful
suggestions
Reviewers Acknowledgments
Ninth Edition Reviewers
Paul Adams, University of Kansas
Kenneth Balazovich, University of Michigan
Tory Hagen, Oregon State University
Marcy Henrick, Appalachian College of Pharmacy
Deborah Heyl-Clegg, Eastern Michigan University
Eighth Edition Reviewers
Kenneth Balazovich, PhD, University of Michigan
Laurent Dejean, California State University at Fresno
Marcy Hernick, Virginia Tech
Holly Huffman, Arizona State University
Mark Kearley, Florida State University
James Knopp, North Carolina State University
Paul Larsen, University of California–Riverside
Gerry Prody, Western Washington University
Sandra Turchi, Millersville University
Seventh Edition Reviewers
Paul D Adams, University of Kansas
Dan Davis, University of Arkansas
Nick Flynn, Angelo State University
Denise Greathouse, University of Arkansas
James R Paulson, University of Wisconsin–Oshkosh
Kerry Smith, Clemson University
Alexandre G Volkov, Oakwood University
We would also like to thank the people at Cengage Learning, who were
essen-tial to the development of this book: Theresa Dearborn, content developer;
Teresa Trego, senior content project manager; Maureen Rosener, product
Alternative Teaching Options Teaching Options T
The order in which individual chapters are covered can be changed to suit the
needs of specific groups of students Although we prefer an early discussion
of thermodynamics, the portions of Chapters 1 and 4 that deal with
thermo-dynamics can be covered at the beginning of Chapter 15 All of the molecular
biology chapters (Chapters 9 through 14) can precede metabolism or can
fol-low it, depending on the instructor’s choice The order in which the material
on molecular biology is treated can be varied according to the preference of
the instructor
Alternate Editions
Loose-Leaf Edition for Biochemistry 9e
ISBN: 978-1-305-96195-1
A loose-leaf (unbound, three-hole-punched) version of Biochemistry 9e, which
can be inserted in a binder, is also available
Acknowledgments
We would like to acknowledge colleagues who contributed their ideas and
critiques of the manuscript Some reviewers responded to specific queries
regarding the text itself We thank them for their efforts and their helpful
suggestions
Reviewers Acknowledgments
Ninth Edition Reviewers
Paul Adams, University of Kansas
Kenneth Balazovich, University of Michigan
Tory Hagen, Oregon State University
Marcy Henrick, Appalachian College of Pharmacy
Deborah Heyl-Clegg, Eastern Michigan University
Eighth Edition Reviewers
Kenneth Balazovich, PhD, University of Michigan
Laurent Dejean, California State University at Fresno
Marcy Hernick, Virginia Tech
Holly Huffman, Arizona State University
Mark Kearley, Florida State University
James Knopp, North Carolina State University
Paul Larsen, University of California–Riverside
Gerry Prody, Western Washington University
Sandra Turchi, Millersville University
Seventh Edition Reviewers
Paul D Adams, University of Kansas
Dan Davis, University of Arkansas
Nick Flynn, Angelo State University
Denise Greathouse, University of Arkansas
James R Paulson, University of Wisconsin–Oshkosh
Kerry Smith, Clemson University
Alexandre G Volkov, Oakwood University
We would also like to thank the people at Cengage Learning, who were
essen-tial to the development of this book: Theresa Dearborn, content developer;
Teresa Trego, senior content project manager; Maureen Rosener, product
Trang 21xx Preface
manager; and Dawn Giovanniello, product director Thank you, Christine Myaskovsky, our intellectual property analyst, and Kathryn Kucharek, our intel-lectual property project manager, at Cengage We also thank Marketing Man-ager Ana Albinson, Content Developer Elizabeth Woods, and Product Assistant Kristina Cannon
Lynn Lustberg of MPS Limited served as our project manager Photo and text research was performed by Rupesh Kumar Jayakumar, Manojkiran Chan-der, and Rashmi Manoharan of Lumina Datamatics
Supporting Materials Please visit http://www.cengage.com/chemistry/campbell/biochemistry9e for information about student and instructor resources for this text
A Final Note from Shawn Farrell
I cannot adequately convey how impossible this project would have been out my wonderful family, who put up with a husband and father who became a hermit in the back office I would also like to thank David Hall, book represen-tative, for starting me down this path, and the late John Vondeling for giving
with-me an opportunity to expand into other types of books and projects
I met Mary Campbell in the mid-1990s when I was asked to collaborate on the fourth edition of this textbook with her She was a fascinating individual and a visionary in this field She believed that biochemistry should be acces-sible not only to the hard-core chemistry and biochemistry majors, but also to the wide range of majors that embrace biochemistry Such was her inspiration for this one-semester text She was very generous with her time and helped me immensely during the process of writing our first edition together She also had a rapier wit and was a hoot to hang out with at science conventions Her sudden passing in May 2014 was a shock to us all, and she will be sorely missed
A Final Note from Owen McDougal
I wish to thank my wife Lynette for her patience and support, may the road rise
to meet you…, my children McKenzie and Riley for reminding me where my priorities belong, and my parents Bob and Bobbie for unconditional support and inspiration to be all I can be
manager; and Dawn Giovanniello, product director Thank you, Christine Myaskovsky, our intellectual property analyst, and Kathryn Kucharek, our intel-lectual property project manager, at Cengage We also thank Marketing Man-ager Ana Albinson, Content Developer Elizabeth Woods, and Product Assistant Kristina Cannon
Lynn Lustberg of MPS Limited served as our project manager Photo and text research was performed by Rupesh Kumar Jayakumar, Manojkiran Chan-der, and Rashmi Manoharan of Lumina Datamatics
Supporting Materials
information about student and instructor resources for this text
A Final Note from Shawn Farrell
I cannot adequately convey how impossible this project would have been out my wonderful family, who put up with a husband and father who became a hermit in the back office I would also like to thank David Hall, book represen-tative, for starting me down this path, and the late John Vondeling for giving
with-me an opportunity to expand into other types of books and projects
I met Mary Campbell in the mid-1990s when I was asked to collaborate on the fourth edition of this textbook with her She was a fascinating individual and a visionary in this field She believed that biochemistry should be acces-sible not only to the hard-core chemistry and biochemistry majors, but also to the wide range of majors that embrace biochemistry Such was her inspiration for this one-semester text She was very generous with her time and helped me immensely during the process of writing our first edition together She also had a rapier wit and was a hoot to hang out with at science conventions Her sudden passing in May 2014 was a shock to us all, and she will be sorely missed
A Final Note from Owen McDougal
I wish to thank my wife Lynette for her patience and support, may the road rise
to meet you…, my children McKenzie and Riley for reminding me where my priorities belong, and my parents Bob and Bobbie for unconditional support and inspiration to be all I can be
Trang 22Biochemistry and Life
c How does biochemistry describe life processes?
Living organisms, such as humans, and even the individual cells of which they are composed, are enormously complex and diverse Nevertheless, certain unifying features are common to all living things from the simplest bacterium to the human being They all
use the same types of biomolecules, and they all use energy As a result,
organisms can be studied via the methods of chemistry and physics Biochemistry can be defined in many ways From the name, it is clear it is the chemistry of life It combines biology and chemistry, and any given instructor may have more of a biology focus, a chemis-try focus, or anything in between
Disciplines that appear to be unrelated to biochemistry can vide answers to important biochemical questions For example, the magnetic resonance imaging (MRI) tests that play an important role
pro-in the health sciences origpro-inated with physicists, became a vital tool for chemists, and currently play a large role in biochemical research The field of biochemistry draws on many disciplines, and its multidis-ciplinary nature allows it to use results from many sciences to answer
questions about the molecular nature of life processes Important
applica-tions of this kind of knowledge are made in medically related fields;
an understanding of health and disease at the molecular level leads
to more effective treatment of illnesses of many kinds
The activities within a cell are similar to the transportation tem of a city The cars, buses, and taxis correspond to the mole-cules involved in reactions (or series of reactions) within a cell The routes traveled by vehicles likewise can be compared to the reac-tions that occur in the life of the cell Note particularly that many vehicles travel more than one route—for instance, cars and taxis can go almost anywhere—whereas other, more specialized modes
sys-of transportation, such as subways and streetcars, are confined to single paths Similarly, some molecules play multiple roles, whereas
others take part only in specific series of reactions Also, the routes operate simultaneously, and we shall see that this is true of the many
reactions within a cell
To continue the comparison, the transportation system of a large city has more kinds of transportation than does a smaller
1-1 Basic Themes 1
Biochemistry and Life 1
Origin of Life on Earth 2
1-2 Chemical Foundations of Biochemistry 2
Amino Acids 2
Carbohydrates 3
Nucleotides 4
Lipids 4
Functional Groups Important in Biochemistry 4
1-3 The Beginnings of Biology 6
The Earth and Its Age 6
Biomolecules 8
Molecules to Cells 12
1-4 The Biggest Biological Distinction—
Prokaryotes and Eukaryotes 16
Spontaneity in Biochemical Reactions 26
Life and Thermodynamics 27
1B BIOCHEMICAL CONNECTIONS
THERMODYNAMICS Predicting Reactions 28
Trang 232 CHAPTER 1 Biochemistry and the Organization of Cells
one Although a small city may have only cars, buses, and taxis, a large city may have all of these plus others, such as streetcars or subways Analogously, some reactions are found in all cells, and others are found only in specific kinds of cells Also, more structural features are found in the larger, more complex cells of larger organisms than in the simpler cells of organisms such
as bacteria
An inevitable consequence of this complexity is the large quantity of terminology that is needed to describe it; learning considerable new vocabu-lary is an essential part of the study of biochemistry You will also see many cross-references in this book, which reflect the many connections among the processes that take place in the cell
Origin of Life on Earth
The fundamental similarity of cells of all types makes speculating on the origins
of life a worthwhile question How did the components of our bodies come to
be and to do the things that they do? What are the molecules of life? Even the structures of comparatively small biomolecules consist of several parts Large biomolecules, such as proteins and nucleic acids, have complex structures, and
living cells are enormously more complex Even so, both molecules and cells must have arisen ultimately from very simple molecules, such as water, methane, carbon
dioxide, ammonia, nitrogen, and hydrogen (Figure 1.1) In turn, these simple molecules must have arisen from atoms
c How did living things originate?
The way in which the Universe itself, and the atoms of which it is posed, came to be is a topic of great interest to astrophysicists as well as other scientists Simple molecules were formed by combining atoms, and reactions of simple molecules led in turn to more complex molecules The molecules that play a role in living cells today are the same molecules as those encountered in organic chemistry; they simply operate in a different context
com-1-2 Chemical Foundations of Biochemistry
Organic chemistry is the study of compounds of carbon and hydrogen and
their derivatives Because the cellular apparatus of living organisms is made
up of carbon compounds, biomolecules are part of the subject matter of ganic chemistry Additionally, many carbon compounds are not found in any organism, and many topics of importance to organic chemistry have little connection with living things We are going to concentrate on the aspects
or-of organic chemistry that we need in order to understand what goes on in living cells
The small molecules found in the cell can usually be lumped into four basic classes We will see these over and over again during our study of biochemistry They are the basic building blocks of life
Amino Acids
The simplest compounds are the amino acids They get their name from the fact that they all contain an amino group and a carboxyl group, as shown in Figure 1.2 Under physiological conditions both the carboxyl group and amino group are ionized (-COO2 and –NH3, respectively) Amino acids can be shown
in various ways, including a structural formula or a ball and stick formula Amino acids have a basic structure where a central carbon atom is bonded to
a carboxyl group, an amino group, a hydrogen, and a variable group, called
organic chemistry the study of compounds of
carbon, especially of carbon and hydrogen and
their derivatives
Trang 241-2 Chemical Foundations of Biochemistry 3
the R group It is the difference between the R groups that makes each
amino acid unique
Carbohydrates
Carbohydrates are compounds made up of carbon, hydrogen, and
oxy-gen, with a general formula of (CH2O)n, where n is at least 3 The
sim-plest forms are called monosaccharides, or sugars The most common
Cell
Bone cell
Plasma membrane Nucleus
Figure 1.1 Levels of structural organization in the human body Note the hierarchy from simple
CH3H
Trang 254 CHAPTER 1 Biochemistry and the Organization of Cells
CH2OH
OH
OH HO
Figure 1.3 Straight chain and cyclic depictions
of glucose, the most common monosaccharide
monosaccharide is glucose, which has the formula C6H12O6, as shown in Figure 1.3 For convenience, sugars are often drawn as a straight chain, but in solution they form cyclic structures Simple sugars often make up much larger polymers and are used for energy storage and structural components
Nucleotides
Nucleotides are the basic unit of the hereditary materials DNA and RNA They also form the molecular currency of the cell, adenosine triphosphate (ATP) A nucleotide is composed of a five-carbon sugar, a nitrogen-containing ring, and one or more phosphate groups The important nucleotide, ATP, is shown in Figure 1.4 It is composed of the nitrogenous base adenine, the sugar ribose, and three phosphates
Lipids
The fourth major group of biochemicals consists of lipids They are the most diverse and cannot be shown with a simple structure common to all lipids However, they all have the common trait that they are poorly soluble in water This is because most of their structure is composed of long chains of hydrocar-bons A simple lipid is palmitic acid, which has 16 carbons There are several ways to depict such a lipid, as shown in Figure 1.5
Another important lipid you have heard of is cholesterol, shown in Figure 1.6 It differs considerably in its structure from palmitic acid, but is still very insoluble in water due to the chains of carbon and the fact that it has only
a single oxygen molecule in it
c Can a chemist make the molecules of life in a laboratory?
Until the early part of the 19th century, there was a widely held belief in “vital forces,” forces presumably unique to living things This belief included the idea that the compounds found in living organisms could not be produced in the laboratory German chemist Friedrich Wöhler performed the critical experi-ment that disproved this belief in 1828 Wöhler synthesized urea, a well-known waste product of animal metabolism, from ammonium cyanate, a compound obtained from mineral (i.e., nonliving) sources
The reactions of biomolecules can be described by the methods of organic chemistry, which requires the classification of compounds according to their
functional groups The reactions of molecules are based on the reactions of their
respec-tive functional groups.
Functional Groups Important in Biochemistry
Table 1.1 lists some biologically important functional groups Note that most
of these functional groups contain oxygen and nitrogen, which are among the most electronegative elements As a result, many of these functional groups are polar, and their polar nature plays a crucial role in their reactivity Some groups that are vitally important to organic chemists are missing from the table because molecules containing these groups, such as alkyl halides and acyl
functional groups groups of atoms that give rise to
the characteristic reactions of organic compounds
P
OH
H H
O–
O CH2
OH O
N N
Figure 1.4 The structure of ATP, an important
nucleotide in energy production.
Palmitic acid
Figure 1.5 The simple lipid palmitic acid, shown
with a structural formula, an abbreviated formula,
and a space-filling model.
Trang 261-2 Chemical Foundations of Biochemistry 5
chlorides, do not have any particular applicability in biochemistry Conversely,
carbon-containing derivatives of phosphoric acid are mentioned infrequently
in beginning courses on organic chemistry, but esters and anhydrides of
phos-phoric acid (Figure 1.7) are of vital importance in biochemistry ATP, a
mol-ecule that is the energy currency of the cell, contains both ester and anhydride
linkages involving phosphoric acid
Important classes of biomolecules have characteristic functional groups
that determine their reactions We shall discuss the reactions of the functional
groups when we consider the compounds in which they occur
Cholesterol
H H
H HO
Figure 1.6 The structure of cholesterol, an important lipid in biological membranes.
Table 1.1 Functional Groups of Biochemical Importance
Amide group
Phosphoric ester group
Phosphoric anhydride group
General Structure
Characteristic Functional Group
Name of Functional Group Example
RCH CH2RCH CHR
R2C CHR
R 2 C CR 2
ROR RNH 2
R 2 NH
R 3 N RSH
CH 3 CH O
CH 3 CCH 3 O
CH 3 COH O
CH 3 COCH 3 O
CH3CN(CH3)2O
O C O
HO OH
O
P OH OH
O C SH N
Trang 276 CHAPTER 1 Biochemistry and the Organization of Cells
1-3 The Beginnings of Biology
The Earth and Its Age
Although humans in general and science fiction writers in particular are cinated by the idea of life on other planets, to date, we are aware of only one planet that unequivocally supports life: our own The Earth and its waters are universally understood to be the source and mainstay of life as we know it A natural first question is how the Earth, along with the Universe of which it is a part, came to be
fas-c How and when did the Earth come to be?
Currently, the most widely accepted cosmological theory for the origin of
the Universe is the big bang, a cataclysmic explosion According to big-bang
cosmology, all the matter in the Universe was originally confined to a paratively small volume of space As a result of a tremendous explosion, this
com-“primordial fireball” started to expand with great force Immediately after the big bang, the Universe was extremely hot, on the order of 15 billion
C
P
O OH
NH2
H2O OH
+
P
O OH OH
H
O OH OH
O O OH
O OH OH
P
O O OH
O
OH O
H
P
O O OH
N HC
N C C
C N CH N
H2O
An ester of phosphoric acid
R
Reaction of two molecules of phosphoric
acid to form an anhydride, which
contains a P-O-P linkage A space-filling
model of the anhydride of phosphoric
acid is shown
2
Reaction of phosphoric acid with a
hydroxyl group to form an ester, which
contains a P-O-R linkage Phosphoric
acid is shown in its nonionized form in
this figure Space-filling models of
phosphoric acid and its methyl ester are
shown The red spheres represent
oxygen; the white, hydrogen; the green,
carbon; and the orange, phosphorus
The structure of ATP (adenosine
triphosphate), showing two anhydride
linkages and one ester
3
1
Figure 1.7 ATP and the reactions for its formation.
Trang 281-3 The Beginnings of Biology 7
(15 3 109) K (Note that Kelvin temperatures are written without a degree
symbol.) The average temperature of the Universe has been decreasing ever
since as a result of expansion, and the lower temperatures have permitted
the formation of stars and planets In its earliest stages, the Universe had a
fairly simple composition Hydrogen, helium, and some lithium (the three
smallest and simplest elements on the periodic table) were present, having
been formed in the original big-bang explosion The rest of the chemical
elements are thought to have been formed in three ways: (1) by
thermonu-clear reactions that normally take place in stars, (2) in explosions of stars,
and (3) by the action of cosmic rays outside the stars since the formation of
the galaxy The process by which the elements are formed in stars is a topic of
interest to chemists as well as to astrophysicists For our purposes, note that
the most abundant isotopes of biologically important elements such as
car-bon, oxygen, nitrogen, phosphorus, and sulfur have particularly stable nuclei
These elements were produced by nuclear reactions in first-generation stars,
the original stars produced after the beginning of the Universe (Table 1.2)
Many first-generation stars were destroyed by explosions called supernovas,
and their stellar material was recycled to produce second-generation stars,
such as our own Sun, along with our solar system Radioactive dating, which
uses the decay of unstable nuclei, indicates that the age of the Earth (and the
rest of the solar system) is 4 billion to 5 billion (4 3 109 to 5 3 109) years The
atmosphere of the early Earth was very different from the one we live in, and
it probably went through several stages before reaching its current
composi-tion The most important difference is that, according to most theories of
the origins of the Earth, very little or no free oxygen (O2) existed in the early
stages (Figure 1.8) The early Earth was constantly irradiated with ultraviolet
light from the Sun because there was no ozone (O3) layer in the atmosphere
to block it Under these conditions, the chemical reactions that produced
simple biomolecules took place
The gases usually postulated to have been present in the atmosphere
of the early Earth include NH3, H2S, CO, CO2, CH4, N2, H2, and (in both
liquid and vapor forms) H2O However, there is less agreement on the
rela-tive amounts of these components, from which biomolecules ultimately
arose Many of the earlier theories of the origin of life postulated CH4 as
Table 1.2 Abundance of Important Elements Relative to Carbon*
Element Abundance in Organisms Abundance in Universe
Trang 298 CHAPTER 1 Biochemistry and the Organization of Cells
the carbon source, but more recent studies have shown that appreciable amounts of CO2 must have existed in the atmosphere at least 3.8 billion (3.8 3 109) years ago
This conclusion is based on geological evidence: The earliest known rocks are 3.8 billion years old, and they are carbonates, which arise from CO2 Any
NH3 originally present must have dissolved in the oceans, leaving N2 in the atmosphere as the nitrogen source required for the formation of proteins and nucleic acids
Biomolecules
c How were biomolecules likely to have formed on the early Earth?
Experiments have been performed in which the simple compounds of the early atmosphere were allowed to react under the varied sets of conditions that might have been present on the early Earth The results of such experi-
ments indicate that these simple compounds react abiotically or, as the word indicates (a, “not,” and bios, “life”), in the absence of life, to give rise to bi-
ologically important compounds such as the components of proteins and nucleic acids Of historic interest is the well-known Miller–Urey experiment
In each trial, an electric discharge, simulating lightning, is passed through
a closed system that contains H2, CH4, and NH3, in addition to H2O Simple organic molecules, such as formaldehyde (HCHO) and hydrogen cyanide (HCN), are typical products of such reactions, as are amino acids, the build-ing blocks of proteins According to one theory, reactions such as these took place in the Earth’s early oceans; other researchers postulate that such reac-tions occurred on the surfaces of clay particles that were present on the early Earth It is certainly true that mineral substances similar to clay can serve as catalysts in many types of reactions Recent theories of the origin of life focus
Figure 1.8 Formation of biomolecules on the early Earth Conditions on early Earth would have been inhospitable for most of today’s life Very little or no oxygen (O2) existed Volcanoes erupted, spewing gases, and violent thunderstorms produced torrential rainfall that covered the Earth The green arrow indicates the formation of biomolecules from simple precursors.
Trang 301-3 The Beginnings of Biology 9
on RNA, not proteins, as the first genetic molecules Proteins are thought
to have developed later in the evolution of the earliest cells This point does
not diminish the importance of this first experiment on abiotic synthesis of
biomolecules
Recent experiments have shown it is possible to synthesize nucleotides
from simple molecules by a pathway that includes a precursor that is neither
a sugar nor a nucleobase, but a fragment consisting of a sugar and a part
of a base This fragment, 2-aminooxazole, is highly volatile and can
vapor-ize and condense so as to give rise to pockets of pure material in reasonably
large amounts In turn, phosphates released by volcanic action can react with
the 2-aminooxazole to produce nucleotides (Figure 1.9) The products
in-clude nucleotides that are not part of present-day RNA, but intense
ultravio-let light, which was present on the early Earth, destroyed those nucleotides,
leaving those found in RNA today
Living cells today are assemblages that include very large molecules, such
as proteins, nucleic acids, and polysaccharides These molecules are larger by
Chemicals present before first living cells
Sugar
Sugar Oxygen
Arabino-C Phosphate
Phosphate RNA NUCLEOTIDE
Phosphate Chemicals present before first living cells
A NEW ROUTE
In the presence of phosphate, the raw materials for nucleobases and ribose first form 2-amino- oxazole, a molecule that contains part of a sugar and part of a C or U nucleobase Further reac- tions yield a full ribose-base block and then a full nucleotide The reactions also produce “wrong” combinations of the original molecules, but after exposure to ultraviolet rays, only the “right”
versions—the nucleotides—survive.
FAILED NUCLEOTIDES
Chemists have long been unable to find a
route by which nucleobases, phosphate and ribose (the
sugar component of RNA) would naturally combine to
generate quantities of RNA nucleotides.
Figure 1.9 Abiotic synthesis of nucleotides The volatile compound 2-aminooxazole is a key
intermediate that eventually gives rise to nucleotides (Copyright © Andrew Swift)
Trang 3110 CHAPTER 1 Biochemistry and the Organization of Cells
many powers of ten than the smaller molecules from which they are built
Hundreds or thousands of these smaller molecules, or monomers, can be linked to produce macromolecules, which are also called polymers The
versatility of carbon is important here Carbon is tetravalent and able to form bonds with itself and with many other elements, giving rise to different kinds
of monomers, such as amino acids, nucleotides, and monosaccharides (sugar monomers)
Proteins and nucleic acids play a key role in life processes In present-day cells,
amino acids (the monomers) combine by polymerization to form proteins, nucleotides (also monomers) combine to form nucleic acids, and the po-
lymerization of sugar monomers produces polysaccharides Polymerization experiments with amino acids carried out under early-Earth conditions have produced proteinlike polymers Similar experiments have been done on the abiotic polymerization of nucleotides and sugars, which tends to happen less readily than the polymerization of amino acids Much of this discussion is spec-ulative, but it is a useful way to start thinking about biomolecules
The several types of amino acids and nucleotides can easily be distinguished from one another When amino acids form polymers, with the loss of water accompanying this spontaneous process, the sequence of amino acids deter-mines the properties of the protein formed Likewise, the genetic code lies in the sequence of monomeric nucleotides that polymerize to form nucleic acids, the molecules of heredity (Figure 1.10) In polysaccharides, however, the order
of monomers rarely has an important effect on the properties of the polymer, nor does the order of the monomers carry any genetic information (Other
aspects of the linkage between monomers are important in polysaccharides, as
we shall see when we discuss carbohydrates in Chapter 16.) Note that all the building blocks have a “head” and a “tail,” giving a sense of direction even at the monomer level (Figure 1.11)
The effect of monomer sequence on the properties of polymers can be
illus-trated by another example Proteins of the class called enzymes display catalytic
activity, which means that they increase the rates of chemical reactions
com-pared with uncatalyzed reactions In the context of the origin of life, catalytic molecules can facilitate the production of large numbers of complex molecules, allowing for the accumulation of such molecules When a large group of related molecules accumulates, a complex system arises with some of the characteris-tics of living organisms Such a system has a nonrandom organization, tends to reproduce itself, and competes with other systems for the simple organic mol-ecules present in the environment One of the most important functions of
proteins is catalysis, and the catalytic effectiveness of a given enzyme depends
on its amino acid sequence The specific sequence of the amino acids present ultimately determines the properties of all types of proteins, including enzymes
monomers small molecules that may bond to
many others to form a polymer
polymers macromolecules formed by the bonding
of smaller units
5' T T C A G C A A T A A G G G T C C T A C G G A G 3'
A strand of DNA
A polypeptide segment Phe Ser Asn Lys Gly Pro Thr Glu
A polysaccharide chain
Figure 1.10 Informational macromolecules
Biological macromolecules are informational
The sequence of monomeric units in a biological
polymer has the potential to contain information
if the order of units is not overly repetitive
Nucleic acids and proteins are informational
macromolecules; polysaccharides are not.
proteins macromolecules formed by the
polymerization of amino acids
nucleic acids macromolecules formed by the
Trang 321-3 The Beginnings of Biology 11
If not for protein catalysis, the chemical reactions that take place in our bodies
would be so slow as to be useless for life processes We are going to have a lot to
say about this point in Chapters 6 and 7
In present-day cells, the sequence of amino acids in proteins is determined
by the sequence of nucleotides in nucleic acids The process by which genetic
information is translated into the amino acid sequence is very complex DNA
(deoxyribonucleic acid), one of the nucleic acids, serves as the coding material The
genetic code is the relationship between the nucleotide sequence in nucleic
acids and the amino acid sequence in proteins As a result of this relationship,
Figure 1.11 Directionality in macromolecules Biological macromolecules and their building
blocks have a “sense” or directionality
Amino acids build proteins by connecting the carboxyl group of
one amino acid with the amino group of the next amino acid.
Polysaccharides are built by linking the first carbon of one sugar
with the fourth carbon of the next sugar
In nucleic acids the 3'-OH of the ribose ring of one nucleotide
forms a bond to the 5'-OH of the ribose ring of a neighboring
nucleotide All these polymerization reactions are accompanied
by the elimination of water
1 2 3
P
O–
N N
COO –
CH2OH
OH O
1 2 3
OH O
4
O
O OCH2P O–
N N
O OCH2P O–
H
H
H
H H H
Trang 3312 CHAPTER 1 Biochemistry and the Organization of Cells
the information for the structure and function of all living things is passed from one generation to the next The workings of the genetic code are no longer completely mysterious, but they are far from completely understood Theories
on the origins of life consider how a coding system might have developed, and new insights in this area could shine some light on the present-day genetic code
Molecules to Cells
c Which came first—the catalysts or the hereditary molecules?
Until recently, our understanding of biochemistry led to a “chicken vs the egg”conundrum when we tried to figure out how life evolved If RNA and DNA are genetic materials that convey the information of heredity and proteins are the molecules that act as catalysts for biochemical reactions, then how did life ever start? Which molecule came first, and how did the other develop?
A discovery with profound implications for discussions of the origin of life
is that RNA (ribonucleic acid), another nucleic acid, is capable of catalyzing its
own processing Until this discovery, catalytic activity was associated exclusively with proteins RNA, rather than DNA, is now considered by many scientists to have been the original coding material, and it still serves this function in some viruses The idea that catalysis and coding both occur in one molecule has pro-vided a point of departure for more research on the origins of life The “RNA world” is the current conventional wisdom, but many unanswered questions exist regarding this point of view
According to the RNA-world theory, the appearance of a form of RNA capable
of coding for its own replication was the pivotal point in the origin of life cleotides can direct the formation of molecules whose sequence is an exact copy
Polynu-of the original This process depends on a template mechanism (Figure 1.12), which is highly effective in producing exact copies but is a relatively slow process
A catalyst is required, which can be a polynucleotide, even the original molecule itself Polypeptides, however, are more efficient catalysts than polynucleotides, but there is still the question of whether they can direct the formation of exact copies of themselves Recall that in present-day cells, the genetic code is based
on nucleic acids, and catalysis relies primarily on proteins How did nucleic acid synthesis (which requires many protein enzymes) and protein synthesis (which requires the genetic code to specify the order of amino acids) come to be? According to this hypothesis, RNA (or a system of related kinds of RNA) origi-nally played both roles, catalyzing and encoding its own replication Eventually, the system evolved to the point of being able to encode the synthesis of more effective catalysts, namely proteins (Figure 1.13) Even later, DNA took over as the primary genetic material, relegating the more versatile RNA to an intermedi-ary role in directing the synthesis of proteins under the direction of the genetic code residing in DNA A certain amount of controversy surrounds this theory, but it has attracted considerable attention
Another key point in the development of living cells is the formation
of membranes that separate cells from their environment The clustering of coding and catalytic molecules in a separate compartment brings molecules into closer contact with each other and excludes extraneous material For reasons we shall explore in detail in Chapters 2 and 8, lipids are perfectly suited
to form cell membranes (Figure 1.14)
Recently, attempts have been made to combine several lines of
reason-ing about the origin of life into a double-origin theory Accordreason-ing to this line of
thought, the development of catalysis and the development of a coding system came about separately, and the combination of the two produced life as we know it The rise of aggregates of molecules capable of catalyzing reactions was one origin of life, and the rise of a nucleic acid–based coding system was another origin
Polynucleotide template
Complementary polynucleotides
Synthesis of new copies of the original strand
Strands separate
The complementary strand acts as a new template strand
Figure 1.12 The role of templates in synthesis of
polynucleotides Polynucleotides use a template
mechanism to produce exact copies of themselves:
G pairs with C, and A pairs with U by a relatively weak
interaction The original strand acts as a template to
direct the synthesis of a complementary strand The
complementary strand then acts as a template for the
production of copies of the original strand Note that
the original strand can be a template for a number
of complementary strands, each of which in turn can
produce a number of copies of the original strand
This process gives rise to a many-fold amplification
of the original sequence (Copyright © 1994 from
The Molecular Biology of the Cell, 3rd Edition, by
A Alberts, D Bray, J Lewis, M Raff, K Roberts, and
J D Watson.)
Trang 341-3 The Beginnings of Biology 13
A catalytic RNA directs its own
replication with the original
nucleotide sequence and shape.
Replication
One RNA molecule in a group
catalyzes the synthesis of all
RNAs in the group.
The RNA sequence becomes a template for the sequence of amino acids in the protein by using the adaptor mechanism.
More catalytic RNAs evolve Some (adaptor RNAs) bind to amino acids.
The adaptor RNAs also engage in complementary pairing with coding RNA.
Coding RNA
Adaptor RNA Growing protein
Catalyst
1
2
3
Figure 1.13 Stages in the evolution of a system of self-replicating RNA molecules At each
stage, more complexity appears in the group of RNAs, leading eventually to the synthesis of
proteins as more effective catalysts (Copyright © 1994 from The Molecular Biology of the Cell, 3rd
Edition, by A Alberts, D Bray, J Lewis, M Raff, K Roberts, and J D Watson.)
Without compartments With compartmentalization by cell membrane
encodes
Protein catalyzes reactions for all RNA
Self-replicating RNA molecules, one of which can direct protein synthesis
The protein made by the cell’s RNA is retained for use in the cell The RNA can be selected
on the basis of its use of a more effective catalyst.
Figure 1.14 The vital importance of a cell membrane in the origin of life Without compartments,
groups of RNA molecules must compete with others in their environment for the proteins they
synthesize With compartments, the RNAs have exclusive access to the more effective catalysts and are
closer to each other, making it easier for reactions to take place (Copyright © 1994 from The Molecular
Biology of the Cell, 3rd Edition, by A Alberts, D Bray, J Lewis, M Raff, K Roberts, and J D Watson )
Trang 3514 CHAPTER 1 Biochemistry and the Organization of Cells
A theory that life began on clay particles is a form of the double-origin theory According to this point of view, coding arose first, but the coding material was the surface of naturally occurring clay The pattern of ions on the clay surface is thought to have served as the code, and the process of crystal growth is thought to have been responsible for replication Nucleotides, then RNA molecules, formed
on the clay surface The RNA molecules thus formed were released from the clay surface and enclosed in lipid sacs, forming protocells In this scenario, protocells exist in a pond with a warm side and a cold side Double-stranded polynucleo-tides are formed on the cold side of the pond on a single-stranded template (Figure 1.15) The protocell moves to the warm side of the pond, where the strands separate The membrane incorporates more lipid molecules The protocell di-vides, with a single-stranded RNA in each daughter cell, and the cycle repeats
In the development from protocells to single cells similar to modern teria, proteins and then DNA enter the picture In this scenario, ribozymes (catalytic RNA molecules) develop and direct the duplication of RNA Other ribozymes catalyze metabolic reactions, eventually giving rise to proteins (Figure 1.16) Eventually, proteins rather than ribozymes catalyze most of the reactions in the cell Still later, other enzymes catalyze the production of DNA, which takes over the primary role in coding RNA now serves as an intermedi-ary between DNA and proteins This scenario assumes that time is not a limit-ing factor in the process In an attempt to study the origins of life, scientists
bac-Protocell divides, and daughter cells repeat the cycle
Nucleotides enter and form comple- mentary strand
Nucleotides
RNA double strand
Daughter cells
5
Membrane incorporates new fatty molecules and grows
Protocell reaches
“maturity”
4
Heat separates the strands
3
2
1
Fatty molecules
f
con vecti
on
Figure 1.15 Hypothetical beginning of replication Simple strings of nucleotides could have formed, perhaps initially lined up on the surface of clay particles (1) On the cold side of the pond, RNA strands become surrounded by simple membranes Nucleotides enter and form complementary strands by base pairing (2) Over time, these protocells gain more molecules and complexity (3) Cells find their way to the warm side of the pond, where the heat allows the RNA molecules to separate (4) The protocell grows and gains more components (5) Finally, the cell
divides, produces daughter cells, and the process repeats (Based on Scientific American, a division
of Nature America, Inc.)
Trang 361-3 The Beginnings of Biology 15
have also attempted to combine the best properties of proteins and nucleic
ac-ids and have created peptide nucleic acac-ids, PNA Evidence shows that the
build-ing blocks of these hybrids could also have formed in the primordial world,
and some theorize that PNA may have been the original molecule that allowed
life to form Currently scientists are attempting to create artificial living cells
EVOLUTION STARTS 1
RNA CATALYSTS 2
METABOLISM BEGINS 3
The first protocell is just a
sac of water and RNA and
requires an external stimulus
(such as cycles of heat and
cold) to reproduce But it
will soon acquire new traits.
Ribozymes—folded RNA cules analogous to protein-based enzymes—arise and take on such jobs as speeding up reproduction and strengthening the protocell’s membrane Consequently, protocells begin to reproduce
RNA is duplicated
Energy
Ribozyme
New strand Ribozyme Other ribozymes catalyze
metabolism—chains of chemical reactions that enable protocells
to tap into nutrients from the environment.
t en
Folded protein
Complex systems of RNA
catalysts begin to translate
strings of RNA letters
(genes) into chains of amino
acids (proteins) Proteins
later prove to be more
efficient catalysts and able
to carry out a variety of tasks.
PROTEINS APPEAR
4
Organisms resembling modern bacteria adapt to living virtually everywhere on earth and rule unopposed for billions of years, until some of them begin to evolve into more complex organisms.
BACTERIAL WORLD 7
Other enzymes begin to make DNA Thanks to its superior stability, DNA takes on the role
of primary genetic molecule.
RNA’s main role is now to act
as a bridge between DNA and proteins.
THE BIRTH OF DNA 6
Figure 1.16 Hypothetical evolution of simple protocells to more complex cells (1) Protocells
were just a simple sac containing simple RNA molecules They could not even replicate without
cycling between cold and warm temperatures (2) In time the cells started replicating on their
own using ribozymes (3) With increasing complexity of RNA molecules, ribozymes begin to
catalyze metabolic pathways (4) As metabolism grows in complexity, RNA begins to be translated
into proteins Proteins prove to be more efficient catalysts (5) Proteins gradually take over
metabolism, replacing most of the functions of ribozymes (6) New enzymes start producing DNA,
which due to its superior stability, replaces RNA as the primary heredity material (7) Organisms
resembling bacteria evolve all over the Earth and rule for a billion years before evolution works to
create more complex organisms (Based on Scientific American, a division of Nature America, Inc.)
Trang 3716 CHAPTER 1 Biochemistry and the Organization of Cells
based on PNA The goal is to demonstrate that under the conditions of the
“primordial soup,” simple molecules could form complex molecules ing the critical functions of catalysis and replication and that these could then form cells capable of dividing
possess-At this writing, none of the theories of the origin of life is definitely established, and none is definitely disproved The topic is still under active investigation It seems highly unlikely that we will ever know with certainty how life originated on this planet, but these conjectures allow us to ask some
of the important questions, such as those about catalysis and coding, that we are going to see many times in this text
1-4 The Biggest Biological Distinction—
Prokaryotes and Eukaryotes
All cells contain DNA The total DNA of a cell is called the genome Individual
units of heredity, controlling individual traits by coding for a functional
pro-tein or RNA, are genes.
The earliest cells that evolved must have been very simple, having the mum apparatus necessary for life processes The types of organisms living to-
mini-day that probably most resemble the earliest cells are the prokaryotes This
word, of Greek derivation (karyon, “kernel, nut”), literally means “before the nucleus.” Prokaryotes include bacteria and cyanobacteria (Cyanobacteria were
formerly called blue-green algae; as the newer name indicates, they are more closely related to bacteria.) Prokaryotes are single-celled organisms, but groups
of them can exist in association, forming colonies with some differentiation of cellular functions
c What is the difference between a prokaryote and a eukaryote?
The word eukaryote means “true nucleus.” Eukaryotes are more complex
or-ganisms and can be multicellular or single celled A well-defined nucleus, set off from the rest of the cell by a membrane, is one of the chief features distin-guishing a eukaryote from a prokaryote A growing body of fossil evidence in-dicates that eukaryotes evolved from prokaryotes about 1.5 billion (1.5 × 109) years ago, about 2 billion years after life first appeared on the Earth Examples
of single-celled eukaryotes include yeasts and Paramecium (an organism
fre-quently discussed in beginning biology courses); all multicellular organisms (e.g., animals and plants) are eukaryotes As might be expected, eukaryotic cells are more complex and usually much larger than prokaryotic cells The diameter of a typical prokaryotic cell is on the order of 1 to 3 µm (1 × 10–6 to
3 × 10–6 m), whereas that of a typical eukaryotic cell is about 10 to 100 µm The distinction between prokaryotes and eukaryotes is so basic that it is now a key point in the classification of living organisms; it is far more important than the distinction between plants and animals
The main difference between prokaryotic and eukaryotic cells is the existence
of organelles, especially the nucleus, in eukaryotes An organelle is a part of the
cell that has a distinct function; it is surrounded by its own membrane within the cell In contrast, the structure of a prokaryotic cell is relatively simple, lacking membrane-enclosed organelles Like a eukaryotic cell, however, a prokaryotic cell has a cell membrane, or plasma membrane, separating it from the outside world The plasma membrane is the only membrane found in the prokaryotic cell In both prokaryotes and eukaryotes, the cell membrane consists of a double layer (bilayer) of lipid molecules with a variety of proteins embedded in it
Organelles have specific functions A typical eukaryotic cell has a cleus with a nuclear membrane Mitochondria (respiratory organelles) and
nu-an internal membrnu-ane system known as the endoplasmic reticulum are also
genome the total DNA of the cell
prokaryotes microorganisms that lack a distinct
nucleus and membrane-enclosed organelles
eukaryotes organisms whose cells have a
well-defined nucleus and membrane-enclosed
organelles
organelle a membrane-enclosed portion of a cell
with a specific function
genes individual units of inheritance
Trang 381-4 The Biggest Biological Distinction—Prokaryotes and Eukaryotes 17
common to all eukaryotic cells Energy-yielding oxidation reactions take place in
eukaryotic mitochondria In prokaryotes, similar reactions occur on the plasma
membrane Ribosomes (particles consisting of RNA and protein), which are the
sites of protein synthesis in all living organisms, are frequently bound to the
en-doplasmic reticulum in eukaryotes In prokaryotes, ribosomes are found free in
the cytosol A distinction can be made between the cytoplasm and the cytosol
Cytoplasm refers to the portion of the cell outside the nucleus, and the cytosol
is the aqueous portion of the cell that lies outside the membrane-bounded
or-ganelles Chloroplasts, organelles in which photosynthesis takes place, are found
in plant cells and green algae In prokaryotes that are capable of
photosynthe-sis, the reactions take place in layers called chromatophores, which are extensions
of the plasma membrane, rather than in chloroplasts
Table 1.3 summarizes the basic differences between prokaryotic and
eukaryotic cells
Prokaryotic Cells
Although no well-defined nucleus is present in prokaryotes, the DNA of the cell
is concentrated in one region called the nuclear region This part of the cell
directs the workings of the cell, much as the eukaryotic nucleus does
c How is prokaryotic DNA organized without a nucleus?
The DNA of prokaryotes is not complexed with proteins in extensive arrays
with specified architecture, as is the DNA of eukaryotes In general, there is
only a single, closed, circular molecule of DNA in prokaryotes This circle of
DNA, which is the genome, is attached to the cell membrane Before a
pro-karyotic cell divides, the DNA replicates itself, and both DNA circles are bound
to the plasma membrane The cell then divides, and each of the two daughter
cells receives one copy of the DNA (Figure 1.17)
In a prokaryotic cell, the cytosol (the fluid portion of the cell outside the
nuclear region) frequently has a slightly granular appearance because of the
presence of ribosomes Because these consist of RNA and protein, they are
also called ribonucleoprotein particles; they are the sites of protein synthesis in all
organisms The presence of ribosomes is the main visible feature of prokaryotic
cytosol (Membrane-bound organelles, characteristic of eukaryotes, are not
found in prokaryotes.)
Every cell is separated from the outside world by a cell membrane, or plasma
membrane, an assemblage of lipid molecules and proteins In addition to the
cell membrane and external to it, a prokaryotic bacterial cell has a cell wall,
which is made up mostly of polysaccharide material, a feature it shares with
eukaryotic plant cells The chemical natures of prokaryotic and eukaryotic cell
nuclear region the portion of a prokaryotic cell that contains the DNA
Table 1.3 A Comparison of Prokaryotes and Eukaryotes
Nucleus No definite nucleus; DNA present but
not separate from rest of cell PresentCell membrane
Mitochondria None; enzymes for oxidation reactions
located on plasma membrane Present
Chloroplasts None; photosynthesis (if present) is
localized in chromatophores Present in green plants
Cell membrane
Ribosomes
Cell wall
Nuclear region (lighter area toward center
of cell)
Figure 1.17 Electron micrograph of a bacterium
A colored electron microscope image of a
typical prokaryote: the bacterium Escherichia coli
(magnified 16,5003) The pair in the center shows that division into two cells is nearly complete.
ribosomes the sites of protein synthesis in all organisms, consisting of RNA and protein
cell membrane the outer membrane of the cell that separates it from the outside world
cell wall the outer coating of bacterial and plant cells
Trang 3918 CHAPTER 1 Biochemistry and the Organization of Cells
walls differ somewhat, but a common feature is that the polymerization of ars produces the polysaccharides found in both Because the cell wall is made
sug-up of rigid material, it presumably serves as protection for the cell
Eukaryotic Cells
Multicellular plants and animals are eukaryotes, as are protista and fungi, but obvious differences exist among them These differences are reflected on the cellular level One of the biggest differences between eukaryotes and prokary-otes is the presence of subcellular organelles
Three of the most important organelles in eukaryotic cells are the nucleus, the mitochondrion, and the chloroplast Each is separated from the rest of the cell by a double membrane The nucleus contains most of the DNA of the cell and is the site of RNA synthesis The mitochondria contain enzymes that cata-lyze important energy-yielding reactions
Chloroplasts, which are found in green plants and green algae, are the sites
of photosynthesis Both mitochondria and chloroplasts contain DNA that fers from that found in the nucleus, and both carry out transcription and pro-tein synthesis distinct from that directed by the nucleus
dif-Plant cells, like bacteria, have cell walls A plant cell wall is mostly made up
of the polysaccharide cellulose, giving the cell its shape and mechanical
stabil-ity Chloroplasts, the photosynthetic organelles, are found in green plants and
algae Animal cells have neither cell walls nor chloroplasts; the same is true of some protists Figure 1.18 shows some of the important differences between typical plant cells, typical animal cells, and prokaryotes
c What are the most important organelles?
The nucleus is perhaps the most important eukaryotic organelle A typical nucleus
exhibits several important structural features (Figure 1.19) It is surrounded by a
nuclear double membrane (usually called the nuclear envelope) One of its
promi-nent features is the nucleolus, which is rich in RNA The RNA of a cell (with the
exception of the small amount produced in such organelles as mitochondria and
chloroplasts organelles that are the sites of
photosynthesis in green plants
nucleus the organelle that contains the main
genetic apparatus in eukaryotes
nucleolus a portion of the nucleus rich in RNA
Endoplasmic reticulum Chloroplast
Figure 1.18 A comparison of a typical animal cell, a typical plant cell, and a prokaryotic cell.
Nucleolus Double membrane Pore in membrane
Immature chloroplasts
Trang 401-4 The Biggest Biological Distinction—Prokaryotes and Eukaryotes 19
chloroplasts) is synthesized on a DNA template in the nucleolus for export to the
cytoplasm through pores in the nuclear membrane This RNA is ultimately
des-tined for the ribosomes Also visible in the nucleus, frequently near the nuclear
membrane, is chromatin, an aggregate of DNA and protein The main eukaryotic
genome (its nuclear DNA) is duplicated before cell division takes place, as in
pro-karyotes In eukaryotes, both copies of DNA, which are to be equally distributed
be-tween the daughter cells, are associated with protein When a cell is about to divide,
the loosely organized strands of chromatin become tightly coiled, and the
result-ing chromosomes can be seen under a microscope The genes, responsible for the
transmission of inherited traits, are part of the DNA found in each chromosome
A second very important eukaryotic organelle is the mitochondrion, which,
like the nucleus, has a double membrane (Figure 1.20) The outer membrane
has a fairly smooth surface, but the inner membrane exhibits many folds called
cristae The space within the inner membrane is called the matrix Oxidation
processes that occur in mitochondria yield energy for the cell Most of the
en-zymes responsible for these important reactions are associated with the inner
mitochondrial membrane Other enzymes needed for oxidation reactions, as
well as DNA that differs from that found in the nucleus, are found in the
inter-nal mitochondrial matrix Mitochondria also contain ribosomes similar to those
found in bacteria Mitochondria are approximately the size of many bacteria,
typically about 1 µm in diameter and 2 to 8 µm in length In theory, they may
have arisen from the absorption of aerobic bacteria by larger host cells
The endoplasmic reticulum (ER) is part of a continuous single-membrane
system throughout the cell; the membrane doubles back on itself to give the
appearance of a double membrane in electron micrographs The endoplasmic
reticulum is attached to the cell membrane and to the nuclear membrane It
occurs in two forms, rough and smooth The rough endoplasmic reticulum is
stud-ded with ribosomes bound to the membrane (Figure 1.21) Ribosomes, which
can also be found free in the cytosol, are the sites of protein synthesis in all
organisms The smooth endoplasmic reticulum does not have ribosomes bound to it.
Chloroplasts are important organelles found only in green plants and green
algae Their structure includes membranes, and they are relatively large, typically
up to 2 µm in diameter and 5 to 10 µm in length The photosynthetic apparatus
is found in specialized structures called grana (singular granum), membranous
bodies stacked within the chloroplast Grana are easily seen through an electron
microscope (Figure 1.22) Chloroplasts, like mitochondria, contain a
characteris-tic DNA that is different from that found in the nucleus Chloroplasts and
mito-chondria also contain ribosomes similar to those found in bacteria
chromatin a complex of DNA and protein found
cristae folds in the inner mitochondrial membrane
matrix the part of a mitochondrion enclosed within the inner mitochondrial membrane
endoplasmic reticulum (ER) a continuous membrane system throughout the cell
single-Grana Double membrane
Figure 1.22 An electron microscope
image of a chloroplast from the alga Nitella
(magnified 60,0003).
Outer membrane Inner membrane
Rough endoplasmic reticulum
Ribosomes Cristae
Matrix
Figure 1.20 Mouse liver mitochondria (magnified 50,0003).
Figure 1.21 Rough endoplasmic reticulum
from mouse liver cells (magnified 50,0003).